Clinical Practice Guidelines for the management of locally advanced ...

Recommendation
Toxicities in the context of what is important to each individual patient should be considered,
as decrements in highly valued faculties for some patients may have a significant impact on
the quality of life and overall adjustment of those individuals and those close to them.
Grade C
5.1.6 Intermittent or continuous androgen deprivation therapy
As stated previously, ADT is associated with a number of toxicities that are quality-of-life impairing
and/or clinically significant and are related to prolonged exposure to castrate level of testosterone.
This is particularly relevant for patients who have a good initial response to therapy that portends the
potential for long-term benefit from ADT. A strategy to potentially ameliorate the toxicity is to use
ADT intermittently (ie withhold when in remission and restart when regrowth occurs). It is also
contended, based on preclinical models, that the cyclical exposure to ADT and testosterone will
prolong the sensitivity to ADT and hence increase the efficacy of ADT. At the time of writing, the
volume of evidence was limited by:
lack of data from reported large well-powered randomised studies, that is, the definitive
studies are yet to be reported and only smaller studies have been reported
inclusion of locally advanced (M0) patients along with patients with evidence of metastatic
disease (M1) and thus poorer prognoses
findings based on subgroup analyses of the use of differing hormonal therapies such as
cyproterone and non-steroidal antiandrogens with LHRH agonists
the use of differing hormonal therapies such as cyproterone and non-steroidal antiandrogens
with LHRH agonists
reporting on progression-free survival whereas overall survival is the more meaningful and
reliable endpoint, especially when balanced by quality-of-life data. Specifically, time to PSA
(biochemical) progression as an endpoint is not clinically relevant.
The current data with all the caveats listed above have some degree of consistency as they suggest
there is no detriment to intermittent versus continuous androgen deprivation. However, the data from
well-powered studies are yet not mature enough to comment on improvement in overall survival and
time to symptomatic progression. At best, the current data suggest there is no decrease in long-term
disease control or overall survival for men with non-metastatic or metastatic disease 44-47 and that there
45, 48-50
may be an improvement in quality of life (potency, hot flushes).
Once the final data are available they will be of major importance as a substantial number of patients
with metastatic prostate cancer commencing ADT are treated with LHRH agonists (as opposed to
orchidectomy) and do achieve a good initial remission with ADT. As such, the more commonly
employed mode of androgen deprivation and the number of patients who would be candidates for an
intermittent approach makes this an approach possibly relevant in clinical practice. Therefore the data
can be directly generalised to the target population with the caveat that larger and better-powered
definitive studies to quantify the benefit still await analysis. The mode of therapy required to
implement intermittent ADT is readily accessible through the PBS (ie LHRH agonists), so if the
definitive datasets confirm its benefit, the data will be directly applicable in the Australian health care
context.
Clinical practice guidelines for the management of locally advanced and metastatic prostate cancer
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